In the next 5 years of the NURSA project, we will carry out a series of advanced data acquisitions that will provide a proteomic atlas for the "systems biology" of signal-regulated NR pathways in vivo. Such highthroughput data acquisition projects are not themselves possible as R01 mechanisms, yet the accumulated data will greatly stimulate hypothesis-driven research in the entire field of nuclear receptor science. We will pursue the isolation and identification of coregulator (CoR) complexes in mouse tissues, improving protocols For generating protein extracts from mouse tissues of liver, adipocytes, uterus and brain for proteomic analyses, and isolating and identify coregulator protein complexes from mouse tissues for analysis by mass spec. We will carry out profiling of post-translational modifications (PTM) of coregulator complexes and we will also profile coordinated PTMs of NR and CoRs following physiologic signaling.